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Amino acids have diverse roles in plant metabolism, and recently amino acid based fertilizers have been used largely in crop production systems. Despite most of these new fertilizers are formulated for foliar application; however, morphophysiological responses of crops to amino acids application have applicationnot yet been well documented. In the present study, foliar application of glycine or glutamine in different concentrations of 0 (distilled water), 250, 500, 1000 mg·L-1, as well as a treatment of 250 mg·L-1 glycine + 250 mg·L-1 glutamine were evaluated on growth of sweet basil (Ocimum basilicum L.) plants. The results showed that foliar application of glycine or glutamine at 1000 mg·L1 showed no improvement in comparison with control for all traits except for leaf Lascorbic acid concentration that showed the highest value under these amino acids treatments. However, foliar application of these amino acids at 250 and particularly 500 mg·L-1 showed promising effect on sweet basil growth. Plant shoot fresh and dry weight, leaf area, leaf SPAD value, and leaf chlorophyll content were improved by foliar application of 500 mg·L-1 glycine or glutamine in comparison with control plants. Foliar application of amino acids increased leaf nitrogen (glutamine 250 and 500 mg·L-1), potassium (glycine 250 mg·L-1), magnesium (glutamine 250 or 500 mg·L-1, glycine 250 mg·L-1, glycine + glutamine; 250 + 250 mg·L-1), iron (glycine and glutamine at 500 mg·L-1 and glutamine at 250 mg·L-1), and zinc (glycine and glutamine at 250 or 500 mg·L-1), whereas the increase in leaf nutrients caused by other treatments was not significantly different from control plants. Leaf calcium concentration was not changed by amino acid treatments. The results indicate that foliar application of moderate to low concentrations of glutamine or glycine can improve sweet basil growth. [ABSTRACT FROM AUTHOR]

Aminochelate are organic-based chelate fertilizers with higher efficiency for agricultural applications. In the present study, foliar application of three organic-based chelate fertilizers, a macro-micro mixture and soil applied NPK were evaluated on French bean growth characteristics under open field in a calcareous soil. The results showed that plant growth, pod yield (79%) and pod quality were improved by application of chelate fertilizers. Growth parameters as plant height, number of leaves and lateral shoots, shoot dry weight, pod number and pod length were significantly increased by foliar application of the chelate fertilizers. The concentrations of nitrogen, potassium and iron in pods and above all in leaves were increased by foliar application of chelate fertilizers compared to control and soil applied NPK. Pod pH and TSS were not influenced by treatments; however, foliar application of the chelate fertilizers resulted in higher titratable acidity (40%), vitamin C (112%) and protein (35%) content of pods. The results indicate that organic-based chelate fertilizers can be effective safer alternatives for simple chemical salts in calcareous soils. [ABSTRACT FROM AUTHOR]

Tomato is a typical plant that has distinct response to different nitrogen forms in hydroponic culture. In addition, it is a well known susceptible plant to ammonium nutrition in hydroponic culture. However, its response to foliar application of nitrogen sources and N-forms has not been well investigated. In the present study, the growth, productivity and fruit quality of tomato was investigated under foliar application of nitrogen from different sources. Ammonium sulfate, urea and calcium nitrate with constant concentration of 100 mM N were weekly sprayed during four months under hydroponic culture system. A water spray treatment was considered as control. The results showed that vegetative growth parameters were significantly affected by N sources in different patterns. The factors such as plant height, leaf area, number of lateral shoots and shoot fresh and dry weight, as well as leaf nitrate reductase activity was significantly reduced by foliar application of ammonium sulfate and to less extent by urea, while there was improvement of these traits by foliar application of calcium nitrate compared to control. However, ammonium sulfate treated plants had the highest leaf SPAD value and leaf N concentrations. Plant fruiting pattern was also influenced by treatments, as ammonium sulfate spray reduced the fruit yield, and fruit vitamin C content, while it increased fruit TSS and titratable acidity. The highest value of yield and vitamin C was recorded in calcium nitrate sprayed plants. [ABSTRACT FROM AUTHOR]

One hundred female Markhoz goats (42±5 kg) were used to investigate the 'male effect' on estrous synchronization and reproductive characteristics of female goat during the breeding season. This was carried out in three separate experiments. In the first experiment, forty female goats were used in 4 groups with different distance from the male goats (i.e. source of pheromone secretion); A1 (1 meter), A2 (12.5 meters), A3 (25 meters) and A4 (50 meters). In the second experiment, thirty female goats were synchronized using CIDR in three groups in the presence or absence of male goats; B1 (the presence of male goat with females during synchronization), B2 (sudden introducing of male goat to females goat during the time of removal of CIDR) and B3 (no male goat during synchronization). In the third experiment, thirty female goats were used in 3 groups; C1 (male goat permanently was presented near to the females during the experiment), C2 (sudden introducing of male to females) and D or control group (no male before mating). The results showed the effect of male goat on estrous synchronization, causing reproductive cycles in early breeding season and increasing incidence of estrous (P<0.05). The male effect improved fertility and kidding rates (P<0.05). Male effect was more pronounced when the distance of unlike sexes decreased (P<0.01). Male effect was also more effective, with sudden introducing of male to female goat (P<0.01). The male effect was more efficient when compared with synchronized female by CIDR in onset of estrous (P<0.05), and increased serum estrogen concentration in the follicular phase (P<0.05). [ABSTRACT FROM AUTHOR]

Ten male Merghoz goats with initial live weights of 29.2 ± 1.2 kg (Mean±SE) were used to investigate the effect of natural changes in photoperiod on dry matter intake (DMI) and reproductive activity during a 365 day study. The bucks were housed in individual pens, under natural daylength condition at west of Iran, Kermanshah (34° 18' N and 47° 3' E and 1420 m above sea level). A diet was offered with an estimated concentration of metabolizable energy and crude protein of 7.9 MJ and 98.8 g per kg dry matter (DM) respectively. Live weight, DMI, and additive daily gain (ADG) of individual animals were recorded weekly. The serum testosterone concentrations were determined in blood samples collected at monthly intervals. During the observation period, semen was collected monthly with the aid of an electro-ejaculator and examined microscopically immediately after collection. The physical parameters of semen and the semen index were recorded. The sexual behavior and testicular size of goats were assessed monthly throughout the study period. The highest DMI was observed during summer (64.3±0.9 g/kg BW0.75) and spring (62.2±2.9 g/kg BW0.75) however, the lowest was recorded in the winter season (54.0±0.9 g/kg BW0.75). The seasonal values of ADG (g/d) ranked spring > summer > winter > autumn. Bucks demonstrated the highest sexual behavior in late summer and, thereafter during autumn, using the lower (P<0.05) number of mounts per ejaculation and a higher frequency (P<0.05) to sniff, approach, and vocalize a doe with estrous status. This was coincided with a higher (P<0.05) level of plasma testosterone (8-10.1 ng/mL) and the best semen quality (semen index: 744-989?106/mL) and quantity (semen volume: 1.1-1.2 mL per ejaculate), higher testis length (13.3- 14.7 cm) and width (6.0-6.1 cm) and scrotal circumference (32.2-35.5 cm). It is concluded that, in Merghoz bucks, the seasonal pattern of DMI and reproductive activity may be attributed to each other as well as photoperiod. [ABSTRACT FROM AUTHOR]

Introduction: Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using 177 Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes., Methods: This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored., Results: Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (K D ) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×10 7 , 7.1×10 8 , and 7.1× 109 [Bq]) indicates that an activity of 7.1×10 8 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues., Discussion: These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Piranfar, Souri, Rahmim and Soltani.)

The intratumoral injection of therapeutic agents responsive to external stimuli has gained considerable interest in treating accessible tumors due to its biocompatibility and capacity to reduce side effects. For the first time, a novel approach is explored to investigate the feasibility of utilizing low-intensity ultrasound in combination with intratumoral injection of drug-loaded magnetic nanoparticles (MNPs) to thermal necrosis and chemotherapy with the objective of maximizing tumor damage while avoiding harm to surrounding healthy tissue. In this study, a mathematical framework is proposed based on a multi-compartment model to evaluate the effects of ultrasound transducer's specifications, MNPs size and distribution, and drug release in response to the tumor microenvironment characteristics. The results indicate that while a higher injection rate may increase interstitial fluid pressure, it also simultaneously enhances the concentration of the therapeutic agent. Moreover, by increasing the power and frequency of the transducer, the acoustic pressure and intensity can be enhanced. This, in turn, increases the impact on accumulated MNPs, resulting in a rise in temperature and localized heat generation. Results have demonstrated that smaller MNPs have a lower capacity to generate heat compared to larger MNPs, primarily due to the impact of sound waves on them. It is worth noting that smaller MNPs have been observed to have enhanced diffusion, allowing them to effectively spread within the tumor. However, their smaller size also leads to rapid elimination from the extracellular space into the bloodstream. To summarize, this study demonstrated that the local injection of MNPs carrying drugs not only enables localized chemotherapy but also enhances the effectiveness of low-intensity ultrasound in inducing tissue thermal necrosis. The findings of this study can serve as a valuable and reliable resource for future research in this field and contribute to the development of personalized medicine., (© 2024. The Author(s).)

Nano-based drug delivery systems hold significant promise for cancer therapies. Presently, the poor accumulation of drug-carrying nanoparticles in tumors has limited their success. In this study, based on a combination of the paradigms of intravascular and extravascular drug release, an efficient nanosized drug delivery system with programmable size changes is introduced. Drug-loaded smaller nanoparticles (secondary nanoparticles), which are loaded inside larger nanoparticles (primary nanoparticles), are released within the microvascular network due to temperature field resulting from focused ultrasound. This leads to the scale of the drug delivery system decreasing by 7.5 to 150 times. Subsequently, smaller nanoparticles enter the tissue at high transvascular rates and achieve higher accumulation, leading to higher penetration depths. In response to the acidic pH of tumor microenvironment (according to the distribution of oxygen), they begin to release the drug doxorubicin at very slow rates (i.e., sustained release). To predict the performance and distribution of therapeutic agents, a semi-realistic microvascular network is first generated based on a sprouting angiogenesis model and the transport of therapeutic agents is then investigated based on a developed multi-compartment model. The results show that reducing the size of the primary and secondary nanoparticles can lead to higher cell death rate. In addition, tumor growth can be inhibited for a longer time by enhancing the bioavailability of the drug in the extracellular space. The proposed drug delivery system can be very promising in clinical applications. Furthermore, the proposed mathematical model is applicable to broader applications to predict the performance of drug delivery systems.

Focused Ultrasound (FUS)-triggered nano-sized drug delivery, as a smart stimuli-responsive system for treating solid tumors, is computationally investigated to enhance localized delivery of drug and treatment efficacy. Integration of thermosensitive liposome (TSL), as a doxorubicin (DOX)-loaded nanocarrier, and FUS, provides a promising drug delivery system. A fully coupled partial differential system of equations, including the Helmholtz equation for FUS propagation, bio-heat transfer, interstitial fluid flow, drug transport in tissue and cellular spaces, and a pharmacodynamic model is first presented for this treatment approach. Equations are then solved by finite element methods to calculate intracellular drug concentration and treatment efficacy. The main objective of this study is to present a multi-physics and multi-scale model to simulate drug release, transport, and delivery to solid tumors, followed by an analysis of how FUS exposure time and drug release rate affect these processes. Our findings not only show the capability of model to replicate this therapeutic approach, but also confirm the benefits of this treatment with an improvement of drug aggregation in tumor and reduction of drug delivery in healthy tissue. For instance, the survival fraction of tumor cells after this treatment dropped to 62.4%, because of a large amount of delivered drugs to cancer cells. Next, a combination of three release rates (ultrafast, fast, and slow) and FUS exposure times (10, 30, and 60 min) was examined. Area under curve (AUC) results show that the combination of 30 min FUS exposure and rapid drug release leads to a practical and effective therapeutic response.

Acquired von Willebrand syndrome (aVWS) develops with various underlying diseases. We herein report an individual with aVWS associated with mucosa-associated lymphoid tissue lymphoma in the lungs complicated by hyperviscosity syndrome, Sjögren's syndrome, and hypothyroidism. This patient developed life-threatening hemorrhaging during a lung biopsy despite transfusion of concentrate of plasma-derived VWF/factor VIII. The use of rituximab caused remission of the lymphoma and hyperviscosity syndrome in parallel with the resolution of aVWS. Thus, lymphoma and hyperviscosity might result in aVWS. Invasive procedures with a risk of bleeding should be avoided in individuals with aVWS.